Blockade of 45Ca2+ influx through the N-methyl-D-aspartate receptor ion channel by the non-psychoactive cannabinoid HU-211

Brain Res. 1993 Sep 17;622(1-2):79-85. doi: 10.1016/0006-8993(93)90804-v.

Abstract

The effects of the synthetic non-psychoactive cannabinoid (+)-(3S,4S)-7-hydroxy-delta 6-tetrahydrocannabinol 1,1-dimethylheptyl (HU-211) on the activity of the N-methyl-D-aspartate (NMDA) receptor/ion channel were examined. HU-211 non-competitively blocks the increase in binding of [3H]N-[1-(2-thienyl)-cyclohexyl]piperidine ([3H]TCP) induced by the polyamines spermine and spermidine or by glutamate and glycine. HU-211 does not, however, affect the direct binding of [3H]glycine and [3H]glutamate to their binding sites on the NMDA receptor, which suggests that the effects of HU-211 are not mediated via the binding sites of glutamate-, glycine- and phencyclidine-like drugs or of polyamines. HU-211 can also block 45Ca2+ uptake through the NMDA-receptor/ion channel in primary cell cultures of rat forebrain. All of the above inhibitory effects of HU-211 on the NMDA-receptor/ion channel activity are stereospecific, since the (-)(3R,4R) enantiomer (HU-210) is ineffective.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites / drug effects
  • Calcium Channels / drug effects*
  • Calcium Radioisotopes
  • Cells, Cultured
  • Dronabinol / analogs & derivatives*
  • Dronabinol / pharmacology
  • Molecular Structure
  • Rats
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / metabolism

Substances

  • Calcium Channels
  • Calcium Radioisotopes
  • Receptors, N-Methyl-D-Aspartate
  • Dronabinol
  • HU 211